The goal of this research is to define some of the physiological and pathological changes that occur in brain due to alcohol abuse. Rats will be used in an experimental model to study the effect of acute and chronic alcohol intoxication. The question whether alcohol selectively affects specific brain structures has never been comprehensively addressed. Most of the observations in man are confused by concomitant nutritional deficiencies. It is not clear whether it is alcohol or malnutrition, or a combination of the two, which is responsible for the well established brain abnormalities associated with chronic alcohol use. The determination of the site of action in vivo is of vital importance to the further understanding of the effect of alcohol as well as providing the basis for the design of future experiments. Therefore, the following will be measured in carefully controlled studies which pay particular attention to nutrition. Regional cerebral metabolism of glucose will be used as a measure of neural function of individual cerebral structures. This will be measured using [6-14C]-glucose as a tracer molecule. Permeability of the blood-brain barrier to four essential nutrients, glucose, phenylalanine, lysine and 3-hydroxybutyrate, will be determined. These are representatives of important transport systems which mediate a delicate balance between supply and need. Disturbances of this balance, which may well occur following alcohol abuse, can have important consequences for cerebral function.